Peter K. Vogt, Ph.D.

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

All our work is directed at a basic understanding of genetic and epigenetic mechanisms that induce oncogenic transformation of cells. With this information, we conduct screens for small molecules that intervene with the activity of newly identified cancer targets. Our current research focuses on three families of cancer targets: protein and lipid kinases, transcriptional regulators and non-coding, antisense RNA.

Among the kinases, phosphatidylinositol 3-kinase (PI3K) has emerged as an important cancer target, because it is frequently mutated in cancer and because most cancers show increased PI3K activity (1). We have characterized the cancer-specific mutations in PI3K (2-5) and continue to explore basic signaling mechanisms that involve this kinase. We are also engaged in the identification and testing of novel specific inhibitors that interfere with oncogenic PI3K.

In the past, we have conducted extensive studies on the oncogenic activity of transcriptional regulators, including Myc, Jun, β-catenin/LEF, and FKHR. Most of our current activity centers on Myc. We have identified small molecules that interfere with the dimerization of Myc and Max (6-9), and these interfere with Myc-induced oncogenic transformation. We have also successfully restricted Myc activity by stabilizing the Max homodimer, making this essential partner less available for Myc. Work on Myc inhibitors continues in collaboration with industry partners.

Many genes generate long, antisense non-coding transcripts. There is evidence that non-coding RNA is critical in the epigenetic regulation of gene activity (10-12). In collaboration with the lab of Kevin Morris at TSRI, we are studying the role of noncoding RNAs in the activation of oncogenes and the silencing of tumor suppressors (13).